The objective of this K23 Award proposal is to investigate the safety and efficacy of ventralis intermedius (VIM) plus ventralis oralis anterior/ventralis oralis posterior (VOA/VOP) deep brain stimulation (DBS) for the treatment of post-traumatic and multiple sclerosis (MS) tremor. Post-traumatic and MS tremors tend to be markedly disabling and refractory to medical therapy. Lesions and deep brain stimulation have had mixed and somewhat disappointing results. Previously, we reported the use of two DBS electrodes (one at the VIM/VOP border and one at the VOA/VOP border) as effective for the treatment of post-traumatic tremor in a single patient, and have since followed up this case with a larger pilot study in four patients. This study will test the hypothesis that two electrodes are better than one for treatment of post-traumatic and MS tremor. Twenty patients will be recruited and randomized into two groups (VIM versus VOAA/OP). All patients will have two electrodes implanted, however, for the first 3 months of the study half of the patients will have VIM DBS, and half VOAA/OP DBS (only one device activated - patient and examiner blinded). Following this blinded period of evaluation, all patients will have both electrodes activated, and at 6 months will be tested in four randomized conditions: VIM DBS on - VOAA/OP DBS off, VIM DBS off - VOAA/OP DBS on, VIM DBS on - VOAA/OP DBS on, and VIM DBS off - VOAA/OP DBS off. Testing will be performed in the clinical research center (CRC) over four days. The study aims not only to evaluate the effects of dual electrode DBS for the treatment of post-traumatic and MS tremor, but also to investigate the effects of each individual electrode, as well as potential side effects of this therapy. It is hoped that this study will result in more effective treatment of medication refractory post-traumatic and MS tremor, and lead to future R01 proposals aimed at the development of innovative applications of DBS technology. The overall proposal has been carefully designed to support the principal investigator's development as a clinical investigator. [unreadable] [unreadable]